Over the past 30 years, thyroid cancer has been on the rise in many populations worldwide. Papillary thyroid cancer is the type seeing the biggest uptick, according to a study published by The Lancet Diabetes & Endocrinology.

Miranda-Filho A, Lortet-Tieulent J, Bray F, et al. Thyroid cancer incidence trends by histology in 25 countries: A population-based study. Lancet Diabetes Endocrinol. 2021;9(4):225–234.

The WHO recently updated its classification of thyroid neoplasms to include new categories and diagnostic criteria, which are outlined for you below.

Baloch ZW, Asa SL, Barletta JA, et al. Overview of the 2022 WHO classification of thyroid neoplasms. Endocr Pathol. 2022;33(1):27–63.

New categories

The changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors as related to thyroid neoplasms begin with a new set of categories that better reflect their pathology, biology, and cellular and molecular makeup.

For example, follicular cell–derived tumors, which make up the majority of thyroid neoplasms, are now categorized as benign, low-risk, or malignant.

Follicular adenoma and variants of adenoma—which include those with papillary architecture—fall under the umbrella of benign follicular cell–derived tumors.

Also within the benign category are the multifocal hyperplastic/neoplastic lesions that most often occur in the multinodular goiter. This entity, described in detail, will now be referred to as thyroid follicular nodular disease (FND).

Low-risk follicular cell–derived neoplasms now include non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Thyroid tumors with undetermined malignant potential and hyalinizing trabecular tumors are also now classified as low-risk.

Within the malignant classification, stratifications are based on the molecular nature and the degree of aggression of the tumors. BRAF-like and RAS-like malignancies are distinguished: papillary thyroid carcinomas (PTCs) and their various morphological subtypes are in the BRAF group, whereas invasive, encapsulated, follicular-variant PTCs and follicular thyroid carcinomas are in the RAS group.

Diagnostic criteria, subtypes, and features of PTC

The 2022 WHO updates include new diagnostic criteria for PTC, the most common malignant thyroid neoplasm, and describe the various PTC subtypes and features.

Now, either papillary growth or invasion is included in its definition.

Molecular studies support the theory that encapsulated, purely follicular-patterned lesions are RAS-like, which lean more toward follicular thyroid carcinomas. As a result, BRAF-like families of malignancies don’t include invasive, encapsulated, follicular-variant lesions.

The PTC subtypes that are the most clinically significant, because of their aggressiveness vs classic PTC, include tall cell, columnar cell, and hobnail. Patients with these PTC types are likely to experience recurrence.

These subtypes can present as fully encapsulated and/or clinically low-stage tumors that don't exhibit certain pathologic features, such as extrathyroidal extension, lymphatic and vascular invasion, and lymph node metastasis.

Classic PTC is recognized by its well-formed papillae lined by tumor cells with nuclei portraying enlargement, peripheral margination of chromatin, clearing of nucleoplasm, and grooves formed by irregular contours, all of which lead to cytoplasmic pseudoinclusions.